1. Field of the Invention
The invention relates generally to compositions and methods for preventing or treating inflammatory bowel disease and particularly to the use of docosahexaenoic acid for preventing or treating feline inflammatory bowel disease.
2. Description of the Related Art
The terms “inflammatory, bowel disease” or “IBD” refer to a group of chronic idiopathic gastrointestinal disorders characterized by inflammatory infiltrates within the lamina propria of the gastrointestinal tract. IBD encompasses segmental granulomatous enterocolitis, lymphoplasmacytic enteritis, eosinophilic gastroenterocolitis, lymphocytic gastroenterocolitis, suppurative enterocolitis, and histiocytic colitis. The lymphoplasmacytic form is probably the most common type of IBD. These specific types of IBD are characterized based on the type of inflammatory infiltrate found in the lamina propria. The inflammatory infiltrates can be quite variable in terms of severity and cell types, with lymphocytes and plasma cells being the most common cell types. Inflammatory infiltrates may involve the stomach, small bowel, and colon. In cats, for example, the stomach and small bowel are affected most often. In many cases, multiple segments of the bowel are involved and clinical signs may be mixed, reflecting the broad distribution of mucosal lesions. The severity of IBD varies from mild clinical signs to life-threatening protein-losing enteropathies.
Mucosal inflammatory infiltrates are responsible for the clinical manifestations of IBD. Mucosal inflammation disrupts normal absorptive processes. Such disruption results in malabsorption and osmotic diarrhea. Altered gut permeability can result in leakage of fluid, protein, and blood into the gut lumen. Malabsorbed fats, carbohydrates, and bile acids result in secretory diarrhea. Inflammatory mediators may also directly trigger intestinal secretion and mucus production by goblet cells. Mucosal inflammatory infiltrates may alter intestinal and colonic motility patters, a mechanism attributed to the influence of prostaglandins and leukotrienes on smooth muscle. Inflammation of the stomach and small bowel stimulates receptors that trigger vomiting. In cats, for example, the most common clinical signs of IBD are chronic vomiting, diarrhea, and weight loss.
The fundamental pathway for the development of IBD involves hypersensitivity. Two related theories attempt to explain the underlying cause for hypersensitivity reactions. The first theory speculates that felines with IBD develop a defect in the intestinal mucosal barrier. Loss of mucosal integrity results in increased gut permeability and hypersensitivity responses to allergens that are normally tolerated. The second theory speculates that IBD results from aberrant immunological responses to luminal antigens. Both potential pathways culminate in release of inflammatory mediators. These substances may further damage the intestinal mucosal surface and set up a cycle of inflammation and loss of barrier function.
Essential fatty acids have specific roles in cell function regulation. For example, the omega-3 eicosapentaenoic acid (EPA), and the omega-6 arachidonic and gamma-linolenic acids are precursors for the synthesis of eicosanoids which are immunoregulatory molecules functioning as local hormones and mediators of inflammation. The eicosanoids synthesized from arachidonic acid (ARA) are proinflammatory compared to eicosanoids produced from eicosapentaenoic and gamma-linolenic acids, and may result in pathologic conditions when produced in excessive amounts. Macrophages are a significant source of eicosanoids, and modulate the intensity and duration of inflammatory and immune responses. The predominant polyunsaturated fatty acid in membrane phospholipids of macrophages and lymphocytes is ARA. Administration of gamma-linolenic or EPA results in the replacement of ARA in the macrophage membrane with eicosapentaenoic or gamma-linolenic acid. The result of such replacement is the production of fewer ARA-derived eicosanoids and more EPA-derived or gamma-linolenic acid-derived eicosanoids, thereby reducing the immunologic response to an inflammatory episode.
A definitive diagnosis of IBD is based on the histopathological examination of mucosal or full-thickness intestinal biopsy specimens collected by endoscopic or surgical techniques. Thus, there is a need for alternative methods for diagnosing feline IBD that are less invasive than obtaining biopsy specimens. There is also a need for new methods and compositions useful for preventing and treating feline IBD.